Multitarget insights into traditional Chinese phytoconstituents against tuberculosis via network pharmacology, molecular docking, and MD simulation

Abstract

Introduction

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a global health threat. Traditional Chinese medicine (TCM), with its extensive use of plant-based compounds, offers a promising alternative for TB treatment. However, the molecular mechanisms underlying the effects of TCM phytoconstituents on TB have not been fully elucidated. This study aims to explore the multitarget therapeutic potential of TCM phytoconstituents for TB management using network pharmacology, molecular docking, and molecular dynamics (MD) simulations.

Methods

Network pharmacology was employed to identify the interactions between phytoconstituents and proteins associated with TB. Molecular docking evaluated compound binding to key TB targets, while MD simulations assessed complex stability and dynamics. Gene expression was analyzed using the eFP server, and mycoCSM predicted bacterial protein responses to compounds, indicating potential drug resistance or susceptibility.

Results

Network pharmacology analysis identified key biological pathways, including the prolactin signalling pathway and the phosphatidylinositol 3-kinase signalling, that may be modulated by these compounds. The docking scores range from -6.5 to -9.0 kcal/mol for Glabroisoflavanone A and B against three major proteins, viz. 1O43, 5XGI, and 6NJS. Both phytoconstituents exhibited a good anti-tubercular sensitivity score. MD simulations (200 ns) further revealed that Glabroisoflavanone A formed the most stable complex with 5XGI.

Discussion

The Glabroisoflavanone A-5XGI complex showed the strongest binding, supported by the most binding free energy (–75.19 ± 4.89 kcal/mol), suggesting a robust interaction. These findings highlight the differential binding and dynamic behavior of phytoconstituents, offering potential insights for therapeutic development.